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Introduction To Toxicology: Richard R. Rediske, Ph.D. Annis Water Resources Institute Grand Valley State University
Introduction To Toxicology: Richard R. Rediske, Ph.D. Annis Water Resources Institute Grand Valley State University
Now
The science that deals with the
adverse effects of chemicals on
living organisms and assesses
the probability of their
occurrence
Outline
• History of Toxicology
• Dose Response
• Types of Toxicants
• Case Studies of alcohol and lead
• The Future
Historical Perspective
“...the appearance of disease in human populations is influenced
by the quality of air, water, and food; the topography of the land;
and general living habits.”
Paracelsus (1493-1541)
The Father of Modern
Toxicology
History
ED50
Potency – concentration to produce an
effect.
CHEMICALS: Major Types of Toxicity
Cancer causing chemicals are assessed by risk
• One mutation has an inherent risk so one molecule of a
toxicant may pose a theoretical risk.
• Organisms have repair functions for protection
• 1:1,000,000 risk is considered acceptable. (note: we
can only measure 1:100 in the laboratory and must
extrapolate the low risk level).
• Toxicity cannot be estimated by high dose experiments
Hormesis – U shaped dose response curve
(nonmonotonic)
• Characterized by a low dose stimulation or beneficial
effect and a high dose inhibitory or toxic effect.
• Essential nutrients, vitamins, ionizing radiation, aspirin,
alcohol
Dose Response Curves
Endocrine disruptors:
• Synthetic or naturally occurring
chemicals that affect the Endocrine or
hormonal system of animals
• May either:
Mimic hormones
Block hormone activities
Directly stimulate or inhibit the
endocrine system
Hormones and Endocrine Disruptors
• Bind to receptor molecules
• Nonmonotonic dose response curves
• Stimulate at low doses
• No increasing effect at high doses due to receptor
saturation
• Very complex reactions and cross reactivity
• Very low doses are significant
• Effect cannot be estimated by high dose toxicity
testing
Endocrine Disruptors
H H
H C C OH H
H
Perceptions About Chemicals
• What drives our perceptions? Are
chemicals bad?
2-24 µg/sq ft
Ingestion
Adults absorb about 6% of ingested lead.
Fasting adults absorb more.
Children absorb much more lead
(30-50% if well fed, and more, if fasting or
malnourished).
It takes >10 years to turn over one half the
body’s stored lead. Bone source slowly
leaches into the blood.
Lead Exposure in utero
walls
windows
doors
bare soil
Lead in dust
porch tracked in
What parts of the body does lead affect?
• Lowered IQ
• Learning disabilities
• Attention deficit and hyperactivity
• Other behavioral issues
• Impaired hearing
• Anemia
• Decreased growth
How to test for lead exposure
• Children should have their
blood tested at ages one and
two.
Voutchkova et al 2009
Schug et al 2012
Estrogen vs Hormonally Active Agents
mindfully.org
Summary
• Toxicology is a complex science based on the
principle of dose and response.
• Environmental exposures further adds to this
complexity.
• Focus more on minimizing hazard by designing
safer chemicals
• Green chemistry can provide solutions!
Summary
Toxicology is a fascinating science that makes biology and
chemistry interesting and relevant.